Bioactive silicates have gained popularity as bone graft substitutes in recent years due to their exceptional ability to bind to host tissues. The current study investigates the effect of changing the metal ion-to-fuel ratio on the properties and biological activity of monticellite prepared via the sol-gel connived combustion technique. Single-phasic monticellite was obtained at 900 °C, without any secondary-phase contaminants for the fuel-lean, stoichiometric, and fuel-rich conditions. SEM and TEM micrographs revealed the porous, spongy morphology of the materials. Because of the reduced crystallite size and higher surface area, the biomineralization of monticellite prepared under fuel-lean conditions resulted in more apatite deposition than those of the other two samples. The results show that the material has a good compressive strength comparable to natural bone, while its brittleness is equivalent to the lower moduli of bone. In terms of antibacterial and antifungal activities, the monticellite bioceramics outperformed the clinical pathogens. It can be used for bone tissue engineering and other biological applications due to its excellent anti-inflammatory and hemolysis inhibitory properties.
The rapid depletion of crude oil and environmental degradation necessitate the search for alternative fuel sources for internal combustion engines. Biodiesel is a promising alternative fuel for compression ignition (CI) engines due to its heat content and combustion properties. Biodiesel blends are used in various vehicles and equipment, such as cars, trucks, buses, off-road vehicles, and oil furnaces. Biodiesel can reduce emissions from CI engines by up to 75% and improve engine durability due to its high lubricity. However, biodiesel has some drawbacks, including a performance reduction and increased nitrogen oxide emissions. Therefore, this study aims to investigate using environmentally available biodiesel in a low-heat rejection engine and an antioxidant additive to enhance the performance and reduce nitrogen oxide emissions. India currently has several biodiesel sources, including mango seed oil, mahua oil, and pongamia oil, which can be effectively utilized in CI engines by adding l-ascorbic acid. The experimental work involves a single-cylinder 4-stroke water-cooled direct injection CI engine with a power output of 5.2 kW. The engine's cylinder head, piston head, and valves are coated with lanthanum oxide using the plasma spray coating technique, with a thickness of 0.5 mm. The coated and uncoated engines are tested with different proportions of mahua oil, mango seed oil, and pongamia oil. The results show that the engine's performance is significantly improved compared to the baseline engine at all loads. Additionally, these biodiesels exhibit a notable reduction in nitrogen oxide emissions when combined with l-ascorbic acid.
Biopolymer-based bioactive hydrogels are excellent wound dressing materials for wound healing applications. They have excellent properties, including hydrophilicity, tunable mechanical and morphological properties, controllable functionality, biodegradability, and desirable biocompatibility. The bioactive hydrogels were fabricated from bacterial cellulose (BC), gelatin, and graphene oxide (GO). The GO-functionalized-BC (GO-f-BC) was synthesized by a hydrothermal method and chemically crosslinked with bacterial cellulose and gelatin using tetraethyl orthosilicate (TEOS) as a crosslinker. The structural, morphological, and wettability properties were studied using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and a universal testing machine (UTM), respectively. The swelling analysis was conducted in different media, and aqueous medium exhibited maximum hydrogel swelling compared to other media. The Franz diffusion method was used to study curcumin (Cur) release (Max = 69.32%, Min = 49.32%), and Cur release kinetics followed the Hixson-Crowell model. Fibroblast (3T3) cell lines were employed to determine the cell viability and proliferation to bioactive hydrogels. Antibacterial activities of bioactive hydrogels were evaluated against infection-causing bacterial strains. Bioactive hydrogels are hemocompatible due to their less than 0.5% hemolysis against fresh human blood. The results show that bioactive hydrogels can be potential wound dressing materials for wound healing applications.
Stearoyl chitosan (SC), derived from the acylation of chitosan, contributes to the efficiency of drug delivery systems because of its structure, which accommodates the drug in a particle. Nonetheless, its role in chemotherapy has been largely unexplored. The present study involves the synthesis of stearoyl chitosan through the reaction of depolymerized chitosan with stearoyl chloride under mild reaction conditions. The resulting compound was subjected to structural analysis utilizing Fourier-transform infrared (FTIR) spectroscopy, 1H NMR, and X-ray diffraction (XRD) spectroscopy. The dispersion of SC molecules in phosphate-buffered saline (PBS) forms SC nanoparticles. The best dispersion of SC in the solution was achieved at a 1:60 chitosan-to-stearoyl chloride weight ratio. Three antimetabolite drugs, methotrexate, pemetrexed, and raltitrexed, were selected to examine the loading efficacy of SC. Pemetrexed had the highest drug-loading value of 36.8% among the three antimetabolites incorporated into SC, along with an encapsulation efficiency of 85.1%. The size of SC loaded with antimetabolites ranged from 225 to 369 nm, and their spherical form was verified via a transmission electron microscope. The in vitro release study showed that SC demonstrated controlled drug release, suggesting that SC nanoparticles have significant promise as a delivery strategy for chemotherapy.
Melilotus indicus (L.) All. is known to have anti-inflammatory and anticancer properties. The present study explored the in vivo skin carcinogenesis attenuating potential of ethanolic extract of M. indicus (L.) All. (Miet) in a 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer model. The ethanolic extract of the plant was prepared by a maceration method. HPLC analysis indicated the presence of quercetin in abundance and also various other phytoconstituents. DPPH radical scavenging assay results showed moderate antioxidant potential (IC50 = 93.55 ± 5.59 μg/mL). A topical acute skin irritation study showed the nonirritant nature of Miet. Data for the skin carcinogenic model showed marked improvement in skin architecture in Miet and its primary phytochemicals (quercetin and coumarin) treated groups. Miet 50% showed comparable effects with 5-fluorouracil. Significant (p < 0.05) anticancerous effects were seen in coumarin-quercetin combination-treated animals than in single agent (coumarin and quercetin alone)-treated animals. Chorioallantoic membrane (CAM) assay results showed the antiangiogenic potential of Miet. Treatment with Miet significantly down-regulated the serum levels of CEA (carcinoembryonic antigen) and TNF-α (Tumor necrosis factor-α). Data for the docking study indicated the binding potential of quercetin and coumarin with TNF-α, EGFR, VEGF, and BCL2 proteins. Thus, it is concluded that Miet has skin cancer attenuating potential that is proposed to be due to the synergistic actions of its bioactive molecules. Further studies to explore the effects of Miet and its bioactive molecules as an adjuvant therapy with low dose anticancer drugs are warranted, which may lead to a new area of research.
Microstructure modification in sodium alginate (NaAlg)-based solid polymer electrolytes by the perchlorate (ClO4-) and acetate (CH3COO-) anions of sodium salts has been reported. ClO4- participates in the structure-breaking effect via inter/intramolecular hydrogen bond breaking, while CH3COO- changes the amorphous phase, as evident from X-ray diffraction studies. The larger size and negative charge delocalization of ClO4- have a plasticizing effect, resulting in a lower glass transition temperature (Tg) compared to CH3COO-. Decomposition temperature is strongly dependent on the type of anion. Scanning electron microscopy images showed divergent modifications in the surface morphology in both electrolyte systems, with variations in salt content. The mechanical properties of the NaAlg-NaClO4 electrolyte systems are better than those of the NaAlg-CH3 COONa system, indicating weak interactions in the latter. Although most of the studies focus on the cation influence on conductivity, the interaction of the anion and its size certainly have an influence on the properties of solid polymer electrolytes, which will be of interest in the near future for sodium ion-based electrolytes in energy storage devices.
Herein, a nonenzymatic detection of paraoxon-ethyl was developed by modifying a glassy carbon electrode (GCE) with gold-silver core-shell (Au-Ag) nanoparticles combined with the composite of graphene with poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT:PSS). These core-shell nanoparticles (Au-Ag) were synthesized using a seed-growth method and characterized using UV-vis spectroscopy and high-resolution transmission electron microscopy (HR-TEM) techniques. Meanwhile, the structural properties, surface morphology and topography, and electrochemical characterization of the composite of Au-Ag core-shell/graphene/PEDOT:PSS were analyzed using infrared spectroscopy, field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), and electrochemical impedance spectroscopy (EIS) techniques. Moreover, the proposed sensor for paraoxon-ethyl detection based on Au-Ag core-shell/graphene/PEDOT:PSS modified GCE demonstrates good electrochemical and electroanalytical performance when investigated with cyclic voltammetry (CV), differential pulse voltammetry (DPV), and chronoamperometry techniques. It was found that the synergistic effect between Au-Ag core-shell nanoparticles and the composite of graphene/PEDOT:PSS provides a higher conductivity and enhanced electrocatalytic activity for paraoxon-ethyl detection at an optimum pH of 7. At pH 7, the proposed sensor for paraoxon-ethyl detection shows a linear range of concentrations from 0.2 to 100 μM with a limit of detection of 10 nM and high sensitivity of 3.24 μA μM-1 cm-2. In addition, the proposed sensor for paraoxon-ethyl confirmed good reproducibility, with the possibility of being further developed as a disposable electrode. This sensor also displayed good selectivity in the presence of several interfering species such as diazinon, carbaryl, ascorbic acid, glucose, nitrite, sodium bicarbonate, and magnesium sulfate. For practical applications, this proposed sensor was employed for the determination of paraoxon-ethyl in real samples (fruits and vegetables) and showed no significant difference from the standard spectrophotometric technique. In conclusion, this proposed sensor might have a potential to be developed as a platform of electrochemical sensors for pesticide detection.
The protein c-Myc is a transcription factor that remains largely intrinsically disordered and is known to be involved in various biological processes and is overexpressed in various cancers, making it an attractive drug target. However, intrinsically disordered proteins such as c-Myc do not show funnel-like basins in their free-energy landscapes; this makes their druggability a challenge. For the first time, we propose a heterodimer model of c-Myc/Max in full length in this work. We used Gaussian-accelerated molecular dynamics (GaMD) simulations to explore the behavior of c-Myc and its various regions, including the transactivation domain (TAD) and the basic helix-loop-helix-leucine-zipper (bHLH-Zipper) motif in three different conformational states: (a) monomeric c-Myc, (b) c-Myc when bound to its partner protein, Max, and (c) when Max was removed after binding. We analyzed the GaMD trajectories using root-mean-square deviation (RMSD), radius of gyration, root-mean-square fluctuation, and free-energy landscape (FEL) calculations to elaborate the behaviors of these regions. The results showed that the monomeric c-Myc structure showed a higher RMSD fluctuation as compared with the c-Myc/Max heterodimer in the bHLH-Zipper motif. This indicated that the bHLH-Zipper motif of c-Myc is more stable when it is bound to Max. The TAD region in both monomeric and Max-bound states showed similar plasticity in terms of RMSD. We also conducted residue decomposition calculations and showed that the c-Myc and Max interaction could be driven mainly by electrostatic interactions and the residues Arg299, Ile403, and Leu420 seemed to play important roles in the interaction. Our work provides insights into the behavior of c-Myc and its regions that could support the development of drugs that target c-Myc and other intrinsically disordered proteins.
Mercury [Hg(II)] contamination is an indefatigable global hazard that causes severe permanent damage to human health. Extensive research has been carried out to produce mercury adsorbents; however, they still face certain challenges, limiting their upscaling. Herein, we report the synthesis of a novel amine-impregnated inverse vulcanized copolymer for effective mercury removal. Poly(S-MA) was prepared using sulfur and methacrylic acid employing the inverse vulcanization method, followed by functionalization. The polyethylenimine (PEI) was impregnated on poly(S-MA) to increase the adsorption active sites. The adsorbent was then characterized byusing Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). FTIR spectroscopy confirmed the formation of the copolymer, and successful impregnation of PEI and SEM revealed the composite porous morphology of the copolymer. Amine-impregnated copolymer [amine@poly(S-MA)] outperformed poly(S-MA) in mercury as it showed 20% superior performance with 44.7 mg/g of mercury adsorption capacity. The adsorption data best fit the pseudo-second-order, indicating that chemisorption is the most effective mechanism, in this case, indicating the involvement of NH2 in mercury removal. The adsorption is mainly a monolayer on a homogeneous surface as indicated by the 0.76 value of Redlich-Peterson exponent (g), which describes the adsorption nature advent from the R2 value of 0.99.
The complex modeling accuracy of gas hydrate models has been recently improved owing to the existence of data for machine learning tools. In this review, we discuss most of the machine learning tools used in various hydrate-related areas such as phase behavior predictions, hydrate kinetics, CO2 capture, and gas hydrate natural distribution and saturation. The performance comparison between machine learning and conventional gas hydrate models is also discussed in detail. This review shows that machine learning methods have improved hydrate phase property predictions and could be adopted in current and new gas hydrate simulation software for better and more accurate results.
Lubricants are important fluids and are commonly used to suppress friction between two metallic surfaces and as a medium for heat transportation. In an industrial plant considered in this study, the base oil mode changes can only be detected based on the kinematic viscosity values obtained using lab analysis. Since the lab analysis data are only available every 8 h, detecting the change in the production modes for 4, 6, and 10 cSt and the transitions among them are significantly delayed, causing unnecessary off-spec products that have to be directed to the slopping tank. In this paper, the innovativeness of the work comes from the idea of trying to unravel the underlying pattern of the plant data that correlate to the changes in the base oil modes and using that to classify hourly the kinematic viscosity values. Hence, a novel industrial application is presented to predict the class of base oil mode change on an hourly basis that can significantly reduce the losses in terms of off spec products and sloping tank wastes. The modes are segregated into three classes based on the values of kinematic viscosity. The classes are C-1 (4 cSt), C-2 (6 cSt), and C-3 (10 cSt). Anything in between the stipulated thresholds is called transition [T-12 (C-1 to C-2), T-21(C-2 to C-1), T-23 (C-2 to C-3), T-31 (C-3 to C-1), and T-32 (C-3 to C-2)]. To unravel the pattern, principal component analysis (PCA) is utilized on 42,000 operating plant data. After a thorough analysis, the third principal component provides the highest correlation to the eight classes of the base oil mode changes [C-1 (4 cSt), C-2 (6 cSt), and C-3 (10 cSt) and the transitions T-12 (C-1 to C-2), T-21(C-2 to C-1), T-23 (C-2 to C-3), T-31 (C-3 to C-1), and T-32 (C-3 to C-2)]. This third principal component is then utilized together with plant process variable values as inputs to four machine learning models, namely, XGBOOST, Random Forest, and CatBoost algorithms to predict the mode of the base oil hourly. The overall comparison analysis shows that utilizing the XGBoost algorithm for the prediction of the eight classes of the base oil modes at a faster hourly rate results in the most consistent classification accuracy of 92.96% for the test set and 89.22% in the deployment set. This capability to predict the mode change in the hourly basis can significantly reduce the losses in terms of off spec products in the production line.
As a result of the transformation of inflexible electronic structures into flexible and stretchy devices, wearable electronics now provide great advantages in a variety of fields, including mobile healthcare sensing and monitoring, human-machine interfaces, portable energy storage and harvesting, and more. Because of their enriched surface functionalities, large surface area, and high electrical conductivity, transition metal nitrides and carbides (also known as MXenes) have recently come to be extensively considered as a group of functioning two-dimensional nanomaterials as well as exceptional fundamental elements for forming flexible electronics devices. This Review discusses the most recent advancements that have been made in the field of MXene-enabled flexible electronics for wearable electronics. The emphasis is placed on extensively established nonstructural features in order to highlight some MXene-enabled electrical devices that were constructed on a nanometric scale. These attributes include devices configured in three dimensions: printed materials, bioinspired structures, and textile and planar substrates. In addition, sample applications in electromagnetic interference (EMI) shielding, energy, healthcare, and humanoid control of machinery illustrate the exceptional development of these nanodevices. The increasing potential of MXene nanoparticles as a new area in next-generation wearable electronic technologies is projected in this Review. The design challenges associated with these electronic devices are also discussed, and possible solutions are presented.
This experimental study reports the kinetic and thermodynamic inhibition influence of sodium chloride (NaCl) on methane (CH4) hydrate in an oil-dominated system. To thoroughly examine the inhibition effect of NaCl on CH4 hydrate formation, kinetically by the induction time and relative inhibition performance and thermodynamically by the hydrate liquid-vapor equilibrium (HLwVE) curve, enthalpy (ΔHdiss) and suppression temperature are used to measure the NaCl inhibition performance through this experimental study. All kinetic experiments are performed at a concentration of 1 wt % under a pressure and temperature of 8 MPa and 274.15K, respectively, whereby for the thermodynamic study, the concentration was 3 wt % by using the isochoric T-cycle technique at the selected range of pressures and temperatures of 4.0-9.0 MPa and 276.5-286.0K, respectively; both studies were conducted using a high-pressure reactor cell. Results show that kinetically, NaCl offers slightly to no inhibition in both systems with/without oil; however, the presence of drilling oil contributes positively by increasing the induction time; thermodynamically, NaCl contributes significantly in shifting the equilibrium curve to higher pressures and lower temperatures in both systems. In the oil system, the contribution of the THI to the equilibrium curve increases the pressure with a range of 0.04-0.15 MPa and reduces the temperature with a range of 1-3 K, which is due to the NaCl presence in the systems that reduces the activity of water molecules by increasing the ionic strength of the solution. At a high pressure of 9 MPa, the NaCl inhibition performance was greater than that at lower pressures <5.5 MPa because, at the high pressure, NaCl increases the activity of water, which means that more water molecules are available to form hydrate cages around gas molecules.
Arsenic in groundwater is a harmful and hazardous substance that must be removed to protect human health and safety. Adsorption, particularly using metal oxides, is a cost-effective way to treat contaminated water. These metal oxides must be selected systematically to identify the best material and optimal operating conditions for the removal of arsenic from water. Experimental research has been the primary emphasis of prior work, which is time-consuming and costly. The previous simulation studies have been limited to specific adsorbents such as iron oxides. It is necessary to study other metal oxides to determine which ones are the most effective at removing arsenic from water. In this work, a molecular simulation computational framework using molecular dynamics and Monte Carlo simulations was developed to investigate the adsorption of arsenic using various potential metal oxides. The molecular structures have been optimized and proceeded with sorption calculations to observe the adsorption capabilities of metal oxides. In this study, 15 selected metal oxides were screened at a pressure of 100 kPa and a temperature of 298 K for As(V) in the form of HAsO4 at pH 7. Based on adsorption capacity calculations for selected metal oxides/hydroxides, aluminum hydroxide (Al(OH)3), ferric hydroxide (FeOOH), lanthanum hydroxide La(OH)3, and stannic oxide (SnO2) were the most effective adsorbents with adsorption capacities of 197, 73.6, 151, and 42.7 mg/g, respectively, suggesting that metal hydroxides are more effective in treating arsenic-contaminated water than metal oxides. The computational results were comparable with previously published literature with a percentage error of 1%. Additionally, SnO2, which is rather unconventional to be used in this application, demonstrates potential for arsenic removal and could be further explored. The effects of pH from 1 to 13, temperature from 281.15 to 331.15 K, and pressure from 100 to 350 kPa were studied. Results revealed that adsorption capacity decreased for the high-temperature applications while experiencing an increase in pressure-promoted adsorption. Furthermore, response surface methodology (RSM) has been employed to develop a regression model to describe the effect of operating variables on the adsorption capacity of screened adsorbents for arsenic removal. The RSM models utilizing CCD (central composite design) were developed for Al(OH)3, La(OH)3, and FeOOH, having R2 values 0.92, 0.67, and 0.95, respectively, suggesting that the models developed were correct.
Influenza remains one of the most widespread infections, causing an annual illness in adults and children. Therefore, the search for new antiviral drugs is one of the priorities of practical health care. Eight isorhamnetin glycosides were purified from Persicaria species, characterized by nuclear magnetic resonance spectroscopy and mass spectrometry and then evaluated as potential agents against influenza virus. A comprehensive in vitro and in vivo assessment of the compounds revealed that compound 5 displayed the most potent inhibitory activity with an EC50 value of 1.2-1.3 μM, better than standard drugs (isorhamnetin 28.0-56.0 μM and oseltamivir 1.3-9.1 μM). Molecular docking results also revealed that compound 5 has the lowest binding energy (-10.7 kcal/mol) among the tested compounds and isorhamnetin (-8.1 kcal/mol). The ability of the isorhamnetin glycosides to suppress the reproduction of the influenza virus was studied on a model of a cell culture and chicken embryos. The ability of active compounds to influence the structure of the virion, as well as the activity of hemagglutinin and neuraminidase, has been demonstrated. Compound 1, 5, and 6 demonstrated the most effective inhibition of virus replication for all tested viruses. Molecular dynamics simulation techniques were run for 100 ns for compound 5 with two protein receptors Hem (1RUY) and Neu (3BEQ). These results revealed that the Hem-complex system acquired a relatively more stable conformation and even better descriptors than the other Neu-complex studied systems, suggesting that it can be an effective inhibiting drug toward hemagglutinin than neuraminidase inhibition. Based on the reported results, compound 5 can be a good candidate to be evaluated for effectiveness in preclinical testing.
Mitragynine is the main psychoactive compound of Mitragyna speciosa Korth. (kratom). This alkaloid could render psychotropic effects and is often misused as a substitute for commercial drugs. Nowadays, the increasing popularity of kratom has led to the development of a rapid and effective detection method. The detection of mitragynine in a biological sample such as urine requires a highly sensitive and specific method due to the complex nature of mitragynine in urine. Enzyme-linked immunosorbent assay (ELISA) is well known as a rapid screening method for biological samples. In this study, a competitive indirect ELISA was successfully developed using MG-22-OCH3 IgG as a detection antibody for mitragynine in human urine. The mitragynine immunoassay showed a limit of detection and a limit of quantification of 0.412 and 1.25 μg/mL, respectively. The measurement range was between 0.01 and 100.0 μg/mL, with a minimal inhibition (IC50) value of 0.152 μg/mL. The developed ELISA was validated using a gold method such as high-performance liquid chromatography-mass spectrometry (HPLC-MS). The percentage of recovery and the coefficient of variation (CV) for the ELISA and LCMS/MS analyses were 84.0-95.70%, 99.20-112.0%, 7.69-9.78%, and 2.86-6.62%, respectively. This indicates that the developed ELISA is a reliable method that can be used as a rapid approach for quantifying mitragynine content in biological samples.
This study investigates the feasibility of hydrogen addition to achieve lower emissions and higher thermal efficiency in an ammonia-biodiesel-fueled reactivity-controlled compression ignition (RCCI) engine. A single-cylinder light-duty water-cooled compression ignition (CI) engine was adapted to run in RCCI combustion with port-injected ammonia and hydrogen as low reactive fuel (LRF) and direct-injected algal biodiesel as high reactive fuel (HRF). In our earlier study, the ammonia substitution ratio (ASR) was optimized as 40%. To optimize fuel and engine settings, hydrogen is added in quantities ranging from 5 to 20% by energy share. The combustion, performance, and emission characteristics were investigated for the trinary fuel operation. The result shows that the 20% hydrogen premixing with 40% ammonia-biodiesel RCCI operation increased the peak cylinder pressure (CP), peak heat release rate (HRR), and cumulative heat release rate (CHRR) by 15.12, 25.15, and 26.68%, respectively. Ignition delay (ID) and combustion duration (CD) were decreased by 15.53 and 11.24%, respectively. The combustion phasing angle was advanced by 4 °CA. The brake thermal efficiency (BTE) was improved by 15.49%, and brake specific energy consumption (BSEC) was reduced by 21.92%. While the nitrogen oxide (NOx) level was significantly increased by about 31.82%, the hydrocarbon (HC), carbon monoxide (CO), smoke, and exhaust gas temperature (EGT) were reduced by 24.53, 28.16, 25.82, and 17.47% as compared to the optimized ASR40% combustion.
Breast cancer (BC) is a malignant neoplasm that begins in the breast tissue. After skin cancer, BC is the second most common type of cancer in women. At the end of 2040, the number of newly diagnosed BC cases is projected to increase by over 40%, reaching approximately 3 million worldwide annually. The hormonal and chemotherapeutic approaches based on conventional formulations have inappropriate therapeutic effects and suboptimal pharmacokinetic responses with nonspecific targeting actions. To overcome such issues, the use of nanomedicines, including liposomes, nanoparticles, micelles, hybrid nanoparticles, etc., has gained wider attention in the treatment of BC. Smaller dimensional nanomedicine (especially 50-200 nm) exhibited improved in vivo effectiveness, such as better tissue penetration and more effective tumor suppression through enhanced retention and permeation, as well as active targeting of the drug. Additionally, nanotechnology, which further extended and developed theranostic nanomedicine by incorporating diagnostic and imaging agents in one platform, has been applied to BC. Furthermore, hybrid and theranostic nanomedicine has also been explored for gene delivery as anticancer therapeutics in BC. Moreover, the nanocarriers' size, shape, surface charge, chemical compositions, and surface area play an important role in the nanocarriers' stability, cellular absorption, cytotoxicity, cellular uptake, and toxicity. Additionally, nanomedicine clinical translation for managing BC remains a slow process. However, a few cases are being used clinically, and their progress with the current challenges is addressed in this Review. Therefore, this Review extensively discusses recent advancements in nanomedicine and its clinical challenges in BC.
The O-acetyl (or acetate) derivative of the Aspidosperma alkaloid Jerantinine A (JAa) elicits anti-tumor activity against cancer cell lines including mammary carcinoma cell lines irrespective of receptor status (0.14 < GI50 < 0.38 μM), targeting microtubule dynamics. By exploiting breast cancer cells' upregulated transferrin receptor 1 (TfR1) expression and apoferritin (AFt) recognition, we sought to develop an AFt JAa-delivery vehicle to enhance tumor-targeting and reduce systemic toxicity. Optimizing pH-mediated reassembly, ∼120 JAa molecules were entrapped within AFt. Western blot and flow cytometry demonstrate TfR1 expression in cancer cells. Enhanced internalization of 5-carboxyfluorescein-conjugated human AFt in SKBR3 and MDA-MB-231 cancer cells is observed compared to MRC5 fibroblasts. Accordingly, AFt-JAa delivers significantly greater intracellular JAa levels to SKBR3 and MDA-MB-231 cells than naked JAa (0.2 μM) treatment alone. Compared to naked JAa (0.2 μM), AFt-JAa achieves enhanced growth inhibition (2.5-14-fold; <0.02 μM < GI50 < 0.15 μM) in breast cancer cells; AFt-JAa treatment results in significantly reduced clonal survival, more profound cell cycle perturbation including G2/M arrest, greater reduction in cell numbers, and increased apoptosis compared to the naked agent (p < 0.01). Decreased PLK1 and Mcl-1 expression, together with the appearance of cleaved poly (ADP-ribose)-polymerase, corroborate the augmented potency of AFt-JAa. Hence, we demonstrate that AFt represents a biocompatible vehicle for targeted delivery of JAa, offering potential to minimize toxicity and enhance JAa activity in TfR1-expressing tumors.